Previous studies performed in our laboratories have shown that the basic pathology in scleroderma consists of the replacement of the subcutaneous tissue by connective tissue. The newly synthesized connective tissue consists of immature collagen fibrils (200-400 A) and large amounts of glycosaminoglycans. The following studies are in progress (a) quantitative and qualitative analysis of dermal glycosaminoglycans in scleroderma and scleredema (b) scleroderma fibroblasts are being cultured in various media to determine cultural requirements, growth curves, platting efficiency, DNA synthesis and morphological characteristics by light and electron microscopy (c) scleroderma fibroblasts cultured in different media will be subjected to metabolic studies using C14 proline and H3 glucosamine as precursors. Synthesis of total proteins, hydroxyproline and glycosaminoglycans, will be estimated at various tissue intervals, both, in the cells and media (d) histologic sections from scleroderma skin are being incubated for 2 and 4 hours with C14 proline and studied by autoradiography to determine degree of uptake at various levels of the skin, including the subcutaneous tissue (e) skin biopsies from systemic scleroderma are being studied by electron microscopy to define the ultrastructural characteristics of various dermal cellular elements.